TY - JOUR T1 - Gamma-Secretase Complexes Regulate the Responses of Human Pancreatic Ductal Adenocarcinoma Cells to Taxanes JF - Anticancer Research JO - Anticancer Res SP - 4999 LP - 5010 VL - 30 IS - 12 AU - TAKEHIKO TASAKA AU - TAKASHI AKIYOSHI AU - KOJI YAMAGUCHI AU - MASAO TANAKA AU - HIDEYA ONISHI AU - MITSUO KATANO Y1 - 2010/12/01 UR - http://ar.iiarjournals.org/content/30/12/4999.abstract N2 - Background/Aim: It was previously reported that γ-secretase inhibitors (GSIs) enhance taxane-induced mitotic arrest and apoptosis in colon cancer cells. To enable the development of taxane-based chemotherapy for pancreatic ductal adenocarcinoma (PDAC), this study investigated the molecular mechanisms by which γ-secretase (GS) complexes regulate taxane sensitivity. Materials and Methods: The effect of GS complexes on taxane-induced apoptosis in PDAC cells was evaluated by a cell cycle analysis. GS complexes were examined with small interference RNAs targeted to GS complex-related genes. Results: GSIs and silencing of presenilin 1 (PS1) did not affect cell proliferation but resulted in enhanced taxane-induced G2/M accumulation and apoptosis. Silencing of the Notch gene did not induce these effects. However, PS2-specific silencing suppressed proliferation and taxane-induced apoptosis. Conclusion: Data from this study indicate that GS complexes regulate the response of PDAC to taxanes through GS-dependent and GS-independent mechanisms. ER -